J B Drummond1,2, B S Soares1, W Pedrosa2, A Ribeiro-Oliveira3. 1. Laboratory of Endocrinology, Federal University of Minas Gerais, Av. Alfredo Balena, 190, Belo Horizonte, Minas Gerais, 30130-100, Brazil. 2. Hermes Pardini Institute, Belo Horizonte, Minas Gerais, Brazil. 3. Laboratory of Endocrinology, Federal University of Minas Gerais, Av. Alfredo Balena, 190, Belo Horizonte, Minas Gerais, 30130-100, Brazil. antoniorojr@gmail.com.
Abstract
PURPOSE: To evaluate factors that could potentially affect the hypothalamic-pituitary adrenal (HPA) axis response to insulin-induced hypoglycemia in children without history or symptoms of adrenal insufficiency and to propose a cut-off value to define a normal response in this population. METHODS: Exploratory single-center study involving 78 children that prospectively underwent insulin tolerance test (ITT) for suspected growth hormone (GH) deficiency. METHODS: Glucose, cortisol, GH, adrenocorticotrophic hormone (ACTH), epinephrine and norepinephrine levels were measured at baseline and after insulin-induced hypoglycemia. Serum cortisol was measured using Access automated immunoassay. RESULTS: Mean (range) basal morning serum cortisol of 8 (2.2-19.5) µg/dL/222 (61-542) nmol/L increased after hypoglycemia to 20.5 (14.6-29.5) µg/dL/570 nmol/L (405-819) nmol/L. Peak serum cortisol levels of 14.6 µg/dL (405 nmol/L) and 15.4 µg/dL (428 nmol/L) corresponded to the 2.5th and 5th percentiles, respectively. Peak serum cortisol correlated with peak plasma epinephrine (r = 0.367; P = 0.0014) but did not correlate with age, BMI-SD or peak serum GH. Children with intact and abnormal GH responses presented similar mean peak serum cortisol levels (20.0 vs. 20.6 µg/dL/555 vs. 572 nmol/L; P = 0.21). CONCLUSION: Our data indicate that the current cut-off to define normal HPA axis response in children after insulin-induced hypoglycemia warrants reevaluation to avoid over-diagnosis of adrenal insufficiency. Our results suggest that peak serum cortisol levels ≥ 15.4 µg/dL (428 nmol/L) in children undergoing ITT might represent a normal cortisol response to stress, regardless of age, BMI or GH secretory capacity.
PURPOSE: To evaluate factors that could potentially affect the hypothalamic-pituitary adrenal (HPA) axis response to insulin-induced hypoglycemia in children without history or symptoms of adrenal insufficiency and to propose a cut-off value to define a normal response in this population. METHODS: Exploratory single-center study involving 78 children that prospectively underwent insulin tolerance test (ITT) for suspected growth hormone (GH) deficiency. METHODS:Glucose, cortisol, GH, adrenocorticotrophic hormone (ACTH), epinephrine and norepinephrine levels were measured at baseline and after insulin-induced hypoglycemia. Serum cortisol was measured using Access automated immunoassay. RESULTS: Mean (range) basal morning serum cortisol of 8 (2.2-19.5) µg/dL/222 (61-542) nmol/L increased after hypoglycemia to 20.5 (14.6-29.5) µg/dL/570 nmol/L (405-819) nmol/L. Peak serum cortisol levels of 14.6 µg/dL (405 nmol/L) and 15.4 µg/dL (428 nmol/L) corresponded to the 2.5th and 5th percentiles, respectively. Peak serum cortisol correlated with peak plasma epinephrine (r = 0.367; P = 0.0014) but did not correlate with age, BMI-SD or peak serum GH. Children with intact and abnormal GH responses presented similar mean peak serum cortisol levels (20.0 vs. 20.6 µg/dL/555 vs. 572 nmol/L; P = 0.21). CONCLUSION: Our data indicate that the current cut-off to define normal HPA axis response in children after insulin-induced hypoglycemia warrants reevaluation to avoid over-diagnosis of adrenal insufficiency. Our results suggest that peak serum cortisol levels ≥ 15.4 µg/dL (428 nmol/L) in children undergoing ITT might represent a normal cortisol response to stress, regardless of age, BMI or GH secretory capacity.
Entities:
Keywords:
Children; HPA axis; Hypoglycemia; Insulin-tolerance test